DPPA4

Chr 3

developmental pluripotency associated 4

Also known as: 2410091M23Rik

NCBI Gene: 55211 ENSG00000121570 UniProt: Q7L190 OMIM: 614125

The DPPA4 protein is a nuclear factor that maintains pluripotency in stem cells and modifies chromatin through its DNA-binding SAP domain, playing an essential role in embryogenesis. Mutations cause a severe developmental disorder with skeletal and lung abnormalities that typically results in late embryonic or early neonatal lethality. The gene shows very low constraint against loss-of-function variants, consistent with the early lethal phenotype observed in mouse models.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a nuclear factor that is involved in the maintenance of pluripotency in stem cells and essential for embryogenesis. The encoded protein has a scaffold-attachment factor A/B, acinus and PIAS (SAP) domain that binds DNA and is thought to modify chromatin. Mice with a homozygous knockout of the orthologous gene die during late embryonic development or within hours after birth. Knockout embryos are normal in size at embryonic day 18.5 but exhibit skeletal and lung tissue abnormalities. This gene, when mutated, is highly expressed in embryonal carcinomas, pluripotent germ cell tumors, and other cancers and is thought to play an important role in tumor progression. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

OMIM ResearchGenerating clinical summary…

LOEUF 0.95

Clinical Summary— DPPA4

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

23 VUS of 26 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.72

OE 0.53 (0.31–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.34Z-score

OE missense 0.92 (0.81–1.06)

150 obs / 162.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.31–0.95)

0≤0.351.4

Missense OE?0.92 (0.81–1.06)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 8 / 15.2Missense obs/exp: 150 / 162.3Syn Z: -1.54

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

VUS23

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	23	23
Likely Benign	1	1
Benign	0	0
Total	24	24

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap DPPA4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →